A rare form of hereditary autism has been discovered and scientists think that it may be treatable with protein supplements since it is linked to an amino-acid deficiency. The genome sequencing of six children with autism revealed mutations in a gene that stops several amino acids from being depleted. Mice lacking this gene developed neurological problems, related to autism spectrum disorder, which can be reversed by dietary changes.
The scientists published their findings in the journal Science. This could be the first treatable form of autism, states Joseph Gleeson, a child neurologist at the University of California, San Diego, and lead author of the study. It could reveal the underlying mechanisms of autism.
However, mutations are likely to account for a very small amount of all autism cases. It won’t have implications for patients in general, and there’s yet no proof that dietary supplements will help the children whose mutations were identified by sequencing the exome.
Three of the children’s parents were first cousins. This makes hunting for the rare recessive mutations that underlie some forms of autism much simpler than among the general population, since the odds are higher that these children will be born with two copies of the recessive mutation.
The team identified mutations that inactivated the enzyme BCKD-kinase, which prevents the body from breaking down amino acids after a meal. The human body cannot synthesize these amino acids, and must obtain them from food.
It’s still a mystery how this amino acid deficiency causes autism. Branched-chain amino acids enter the brain through specialized transporters through the blood-brain barrier. The transporter proteins also shuttle other large amino acids into the brain. When levels of the amino acids are low, more of these molecules are allowed through.
Gleeson hypothesizes that the symptoms of this kind of autism are caused by low levels of branched-chain amino acids, high levels of other amino acids, or a combination of these two factors.
This chemical imbalance is treatable in mice when they were put on a diet enriched in branched-chain amino acids. The children’s imbalance was also treated in this fashion, but there is yet no proof that their autism symptoms got better.
In a properly controlled clinical trial, the researchers hope to see whether dietary supplements ease the children’s symptoms.
Reference: “Mutations in BCKD-kinase Lead to a Potentially Treatable Form of Autism with Epilepsy” by Gaia Novarino, Paul El-Fishawy, Hulya Kayserili, Nagwa A. Meguid, Eric M. Scott, Jana Schroth, Jennifer L. Silhavy, Majdi Kara, Rehab O. Khalil, Tawfeg Ben-Omran, A. Gulhan Ercan-Sencicek, Adel F. Hashish, Stephan J. Sanders, Abha R. Gupta, Hebatalla S. Hashem, Dietrich Matern, Stacey Gabriel, Larry Sweetman, Yasmeen Rahimi, Robert A. Harris, Matthew W. State and Joseph G. Gleeson, 6 September 2012, Science.